We are broadly interested in manipulating the extracellular matrix (ECM) microenvironment to induce cell fate commitment or to modulate other cellular functions. Some of the ECM properties of interest include the ECM chemical composition, topographical patterning, and rigidity. We are developing oriented nano-scale and micro-scale biomaterials that guide cell organization and modulates cell function. We hypothesize that spatially patterned biomaterials can alter cytoskeletal tension and chromatin remodeling to influence cell fate. We are also engineering high-throughput approaches for testing combinatorial ECM compositions and rigidities that favor cell fate commitment of induced pluripotent stem cells towards cardiovascular lineages. Our recent R01-funded project focuses on the use of engineered ECM mimetics with controllable chemical ligands, stiffness, and stress relaxation properties.

Mechanotransduction Pathways that Induce Cell Fate Commitment

Using customizable ECM microenvironments, we are interested in studying mechanotransduction pathways that induce cell fate commitment or function. Some of the mechanotransduction pathways of interest include those that are activated by integrins, focal adhesions, and actin-binding proteins. Current projects include mechanotransduction pathways that are involved cardiovascular differentiation of induced pluripotent stem cells, direct transdifferentiation of fibroblasts into cardiovascular lineages, effects of stiffness on endothelial-to-mesenchymal transition, and reprogramming of fibroblasts into induced pluripotent stem cells.

Tissue Engineering and Regenerative Medicine

By gaining fundamental insights in the role of ECM-mediated mechanotransduction pathways on cell fate commitment, we will engineer three-dimensional vascular conduits, cardiac patches, and skeletal muscle grafts with physiologically relevant cellular and ECM compositions. We are also working with industry partners to engineer nanofibrillar scaffolds that can induce angiogenesis or lymphangiogenesis.

Imaging and Devices Technology

In order to study the function of cells and/or engineered constructs in vivo, we have engineered devices or platforms to overcome existing technological limitations. We are engineering microscale high-throughput arrayed platforms for studying combinatorial extracellular matrix proteins on stem cell fate in a facile manner. To study the role of hemodynamic shear stress gradients on cell behavior, we developed a novel fluid flow device that recapitulates shear stress gradients and disturbed flow. In another example, we have tested the utility of near infrared fluorophores in the second window (~1400nm emission) as angiographic contrast dyes to visualize blood flow, blood perfusion, and microvasculature at high architectural resolution in mice. These technological developments together enable us to study cell biology and pathophysiology of limb ischemia in unprecedented ways.